Development of therapeutic method by MR fluorescence image by Gd-DTPA-fluorescent dye loading polymeric micelle

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10570
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Kaida Sachiko 滋賀医科大学, 医学部, 助教 (70710234)
• Co-Investigator(Kenkyū-buntansha): 仲 成幸 滋賀医科大学, 医学部, 非常勤講師 (10359771) ; 谷 眞至 滋賀医科大学, 医学部, 教授 (60236677)
• Research Collaborator: Cabral Horacio 東京大学, 工学部, 准教授 (10533911)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: MRI造影剤 / 蛍光色素 / drug delivery system / polymer

Outline of Final Research Achievements

Gd-DOTA / IR-820 polymer was prepared by combining the MRI positive contrast agent Gd-DOTA with the fluorochrome IR-820 and characterized. It was stable in vivo with a diameter of about 30 nm, and had an T1 shortening effect of about 8 times that of Gd-DOTA. A rat hepatocellular carcinoma (N1S1) model was prepared, the same polymer was administered from a catheter placed in the tail vein, and accumulation in the tumor was measured over time by MRI, and accumulation of fluorescent dye in each organ was determined by Photodynamic Eye (Hamamatsu Photonics). Gd-DOTA / IR-820 polymer had a significant tumor imaging effect in a rat hepatocellular carcinoma model compared with the Gd-DOTA administration group at the same concentration.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

腫瘍組織では新生血管の透過性亢進と不十分なリンパ系ドレナージのためにナノサイズの高分子薬物が集積しやすくなっている（Enhance Permeability and Retention：EPR効果）。この性質を用いた高分子ドラッグによるDrug Delivery System(DDS)が期待されているが、体内での薬物分布が不明であり副作用の懸念も大きい。今回の研究は、癌に対する安全で効果的な診断薬開発を目的とし、MRI造影剤と蛍光色素を含有した高分子ポリマーを独自に開発しvisible-DDSを可能とした。本技術を応用することで、今後さらに診断能力の高く無害な薬剤の開発につながると思われる。